Platelet Aggregation Inhibitors and Anticoagulants in Gastroenterological and Visceral Surgical Procedures

Abstract

Background

The proper management of patients being treated with platelet aggregation inhibitors or anticoagulant drugs is a common clinical problem for both elective and emergency procedures in gastroenterology and visceral surgery. The essential matters that must be kept in mind in this situation are the hemorrhagic risk of the procedure, the indication for anticoagulation, and the pharmacology of anticoagulant drugs and platelet aggregation inhibitors.

Method

This review is based on publications retrieved by a selective search in PubMed and on the guidelines of the relevant specialist societies.

Results

Nearly all procedures in gastroenterology and visceral surgery can be performed under monotherapy with acetylsalicylic acid. Other platelet aggregation inhibitors, such as clopidogrel or prasugrel, or anticoagulant drugs generally do not need to paused before diagnostic endoscopic procedures with a low risk of bleeding (<1.5%), but they must be paused before procedures in gastroenterology and visceral surgery where the risk of bleeding is high (≥ 1.5%). Bridging with heparin is reserved for patients with a very high risk of thromboembolism (≥ 5%).

Conclusion

Knowledge of the current recommendations on the management of anticoagulants before gastroenterological and visceral surgical procedures gives the clinician a well-founded means of dealing with this complex and common clinical situation.

It has been estimated, on the basis of the number of daily doses prescribed in Germany within the statutory health insurance system, that at least 2.5 million patients were treated with an oral anticoagulant drug (OAC) and at least 500 000 patients were treated with a platelet aggregation inhibitor (PAI) in Germany in 2020 (1).

Prescription frequency.

At least 2.5 million patients were treated with an oral anticoagulant drug (OAC) and at least 500 000 patients were treated with a platelet aggregation inhibitor (PAI) in Germany in 2020.

80% of the prescribed OAC daily doses are direct oral anticoagulants (DOAC; apixaban, dabigatran, edoxaban, rivaroxaban). The percentage of patients receiving vitamin K antagonists ([VKA], in Germany mainly phenprocoumon) has markedly declined in comparison with the previous years.

Hemorrhagic complications are the most frequent and most relevant side effect of PAI and OAC. For Marcumar, the manufacturer’s information for physicians gives a 10% rate of minor bleeding, such as epistaxis, and a 0.1% to less than 1% rate of major bleeding such as intracranial hemorrhage. Patients with medication-induced bleeding are often treated in hospitals and emergency rooms (2, 3).

Methods

Complications.

Hemorrhagic complications are the most frequent and most relevant side effect of oral anticoagulant drugs and platelet aggregation inhibitors. Patients with medication-induced bleeding are often treated in hospitals and emergency rooms

This review is based on publications retrieved by a selective search in PubMed and on the guidelines of all relevant specialty societies, including the DGVS (Deutsche Gesellschaft für Verdauungs- und Stoffwechselerkrankungen – German Society for Digestive and Metabolic Diseases), the ESGE (European Society of Gastrointestinal Endoscopy), the DGK (Deutsche Gesellschaft für Kardiologie – German Society for Cardiology), and the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin – German Society for Anesthesiology and Intensive Care Medicine).

Learning objectives

Readers of this article will learn the safe management of patients taking OAC and PAI, including those who may later undergo visceral procedures that are potentially associated with acute hemorrhagic complications. With respect to the benefits and risks of these drugs, treating physicians are required to:

• know the risk of bleeding associated with various visceral medical procedures;

• be able to assess the thrombotic and thromboembolic risk associated with pausing anticoagulation/PAI depending on the indication for the drug;

• and, in case of acute bleeding, know how to avoid an excessive increase of the thromboembolic risk induced by pausing or antagonizing the drug.

Results

Anticoagulation and Antiplatelet Therapy in Visceral Medicine

Patients taking OAC or PAI who are about to undergo visceral medical procedures generally fall into one of the following three categories::

• the patient is on OAC or PAI and to undergo an elective visceral medical procedure (e.g., endoscopy or cholecystectomy);

• the patient is on OAC or PAI and is suffering from an acute gastrointestinal hemorrhagic complication;

• the patient is on OAC or PAI and urgently needs a visceral medical procedure carrying an increased procedural risk of bleeding (e.g., endoscopic retrograde cholangiopancreaticography with sphincterotomy, liver transplantation).

In all of these situations, the individual risk of bleeding and the associated complications, which may be life-threatening, must be weighed against the risk of thrombotic and thromboembolic complications (4).

Elective visceral medical procedures

Careful weighing of opposing risks.

For all patients taking OAC or PAI who are about to undergo visceral medical procedures, the individual risk of bleeding and the associated complications, which may be life-threatening, must be weighed against the risk of thrombotic and thromboembolic complications

Regarding the general hemorrhagic risk, there is an internationally standardized classification into interventions with a high risk of bleeding (> 1.5%) and those with a low risk (< 1.5%= (4–6). The risk of bleeding that is quoted here generally applies to patients who are not on OAC or PAI; taking these drugs is thought to elevate the risk (4, 7).

The main types of endoscopic intervention are listed by category in Box 1. Endoscopic procedures and visceral surgery are dealt with differently and will be considered separately below.

BOX 1. Risk stratification of endoscopic procedures (adapted from [4]).

Procedures with a high risk of bleeding (> 1.5% in 30 days)

• polypectomy > 1 cm

• endoscopic retrograde cholangiopancreaticography (ERCP) with sphincterotomy or papillectomy

• endosonography with biopsy/intervention

• variceal therapy

• dilation/bougienage

• peroral endoscopic myotomy (POEM)

• endoscopic submucosal dissection

• endoscopic mucosal resection

• gastropexy, percutaneous endoscopic gastrostomy (PEG)

• endoscopic hemostasis, except argon plasma coagulation (APC) therapy

• radiofrequency ablation (RFA), laser ablation

• therapeutic balloon enteroscopy

Prodecures with a low risk of bleeding (< 1.5% over 30 days)

• diagnostic endoscopy, including mucosal biopsy

• ERCP without sphincterotomy, including stent exchange

• endosonography without biopsy

• implantation of stents in the intestinal tract (without dilatation/bougienage)

• diagnostic balloon enteroscopy

• capsule endoscopy

Elective endoscopic procedures

In general, procedures that are mainly diagnostic (e.g., endoscopy including forceps biopsy, endosonography without fine-needle aspiration [FNA]), and also therapeutic procedures without mucosal injury (e.g., gastrointestinal stent replacement without dilatation, endoscopic retrograde cholangiopancreaticography [ERCP] with stent replacement but without sphincterotomy) are considered to carry a low risk of bleeding (8). In contrast, most therapeutic procedures (e.g., ERCP with sphincterotomy, colonoscopy with snare polypectomy > 1 cm) carry a high risk of bleeding (4, 6).

For all procedures except papillectomy (4), monotherapy with acetylsalicylic acid (ASA) for prophylaxis against cardiovascular events should generally not be paused, regardless of whether a high or low procedural risk is present. ASA monotherapy does not elevate the risk of periprocedural bleeding to any clinically relevant extent; pausing ASA monotherapy, even for a short time, markedly elevates the rates of cardiovascular and cerebral events (the increase in risk is more than threefold, and much higher for patients with indwelling coronary stents) (9– 11).

Endoscopic procedures with a low risk of bleeding

Endoscopic procedures.

Stratification of the risk of bleeding associated with an endoscopic procedure is essential for determining the proper periprocedural management of OAC and platelet aggregation inhibitors.

Before an endoscopic procecure is performed, the procedure should be classified by the risk of bleeding, as detailed in Box 1. If the risk is low, P2Y12 antiplatelet drugs should not be paused (this also applies to dual antiplatelet therapy [DAPT] in combination with with ASA), and patients taking direct oral anticoagulant drugs (DOAC) should only the morning dose on the day of the intervention (this applies to all of the approved substances) (4). This recommendation is owing to the pharmacokinetics of DOACs: their peak effect, 2–6 hours after ingestion, would otherwise often coincide with the intervention (12). Fewer patients than in the past are now taking phenprocoumon; in these patients, the International Normalized Ratio (INR) value should be checked five days before the procedure to ensure that it is in the target range. If it is markedly higher, phenprocoumon should be paused and checked immediately before the procedure to ensure that it has returned to the low therapeutic range. Good evidence shows that endoscopic biopsies can be safely performed under treatment with vitamin K antagonists and/or DAPT, with relevant bleeding complications in less than one in a thousand cases (8). There are only scant data on mucosal biopsies under DOAC; skipping the morning dose on the day of the procedure is recommended (13, 14).

Endoscopic procedures with a high risk of bleeding

If a high-risk endoscopic procedure is to be performed, further stratification of the thrombotic risk of the individual patient is needed, as there would be an unacceptable risk of intra- and postprocedural bleeding complications if OAC or PAI were to be continued. In this situation as well, there is a binary classification into high or low risk for thrombosis or thromboembolism, which differs for OAC and PAI (Boxes 2 and 3). The recommendations for the management of these drugs before high-risk endoscopic procedures are given in Figure 1, broken down by type of treatment and by risk.

BOX 2. The risk of arterial thrombosis/stent thrombosis (modified from [34]).

High risk (incidence 3–5%), (36, 37)

• acute coronary syndrome (STEMI or NSTEMI) within the past 12 months

• coronary stents in the first 6–12 months after implantation (for drug eluting stents, mainly in the first 3 months)*

Low risk (incidence < 1%), (36, 37)

• peripheral arterial occlusive disease (PAOD) without stenting

• primary and secondary prevention of stroke

• stable coronary artery disease (CAD) without a stent, or at least 6–12 months after stent implantation

* Determination of the individual risk in consultation with the treating cardiologists; STEMI, ST-elevation myocardial infarction; NSTEMI, non-ST-elevation myocardial infarction

BOX 3. Thromboembolic risk in common clinical situations (modified according to [4]).

Low risk of thromboembolism (incidence < 5 %)

• > 3 months after venous embolism

• biological heart valve

• atrial fibrillation without further risk factors (CHADS₂ ≤ 4)

High risk of thromboembolism (incidence ≥ 5 %)

• < 3 months after venous embolism

• mechanical heart valve (especially mitral valve)

• atrial fibrillation + mitral stenosis

• atrial fibrillation + artificial heart valve

• atrial fibrillation + status post stroke/TIA > 3 months ago, and any three of the following: congestive heart failure, hypertension, age > 75 years, diabetes mellitus

• severe thrombophilia (factor V Leiden homozygous, JAK2 mutation, antiphosholipid syndrome, severe protein C/protein S/antithrombin deficiency)

Figure 1.

Algorithm for the management of PAI and OAC for endoscopic procedures with a high risk of bleeding (modified from [4, 17]).

*¹Assessment of bleeding risk: Table 1; *²assessment of thrombotic risk: Table 2; *³ assessment of thromboembolic risk: Table 3

ASA, acetylsalicylic acid; DOAC, direct oral anticoagulants; DAPT, dual antiplatelet therapy including a P2Y12 inhibitor (clopidogrel, prasugrel, ticagrelor); eGFR, estimated glomular filtration rate; INR, international normalized ratio; LMWH, low molecular weight heparin; VKA, vitamin K antagonist

The peri-interventional management of PAI in endoscopic procedures with a high risk of bleeding

Periprocedural management for endoscopy.

Vitamin K antagonists and platelet aggregation inhibitors need not be paused before endoscopic procedures carrying a low risk of bleeding, but direct oral anticoagulants should not be taken on the morning of the procedure.

The management of ASA.

ASA need not be paused, even before procedures with a high risk of bleeding.

Patients with stable coronary artery disease or peripheral/cerebral occlusive disease are not at high risk of a cardiovascular complication from the temporary discontinuation of DAPT. For such patients, DAPT or monotherapy with a P2Y12 inhibitor should be stopped 3–7 days before the intervention (depending on half-life and potency; 5 days for clopidogrel, 7 days for prasugrel, 3–5 days for ticagrelor), and ASA monotherapy should be maintained or adapted (15, 16). In contrast, for patients with unstable coronary artery disease or those who have received a coronary stent in the past 12 months, PAI should only be paused after consultation with the interventional cardiologist, and the intervention may have to be postponed. Especially in patients with a prior myocardial infarction (either an ST-elevation myocardial infarction [STEMI] or a non-ST-elevation myocardial infarction [NSTEMI]) within the last twelve months, an interdisciplinary consideration of the risks and benefits in consultation with the interventional cardiologist is essential (17). A standardized approach to all such patients would be of little use, as each case requires the detailed consideration of all options, with individualized risk assessment; the options may include pausing or postponing the anticoagulant drug, bridging with heparin, or performing the procedure without pausing the drug and accepting the increased hemorrhagic risk.

The peri-interventional management of OAC in endoscopic procedures with a high risk of bleeding

The management of P2Y12 inhibitors.

P2Y12 inhibitors should generally be paused before procedures with a high risk of bleeding; in patients who are at high cardiovascular risk, the decision whether to pause the drug should be taken after an interdisciplinary risk evaluation.

Analogously, patients who are under treatment with OAC are first evaluated for the risk of thrombembolic complications. For example, in patients with a history of thrombosis more than 3 months in the past, or atrial fibrillation without other significant accompanying diseases, oral anticoagulation can be temporarily paused with a relatively low risk. On the other hand, in patients with a mechanical heart valve or a recent history of pulmonary embolism, a marked drop in the INR over the course of a few days would carry an unacceptably high risk of a fatal event (18, 19). An algorithm for the management of OAC for endoscopic procedures with a high risk of bleeding, depending on the thrombotic/thromboembolic risk, is shown in Figure 1. It must be noted, in this connection, that bridging of anticoagulation with heparin is generally not recommended (4), as randomized trials have shown that this increases the periprocedural bleeding risk in patients without atrial fibrillation (AF) without preventing additional thromboembolic complications (20, 21). Because these studies primarily included patients with AF who had a low thromboembolic risk (CHADS₂ or CHA₂DS₂VASc), the findings do not apply to patients with high thromboembolic risk; thus, heparin bridging is usually performed in patients at high thromboembolic risk (AF with valve disease and/or valve replacement, AF with a CHADS₂ score ≥ 5, a mechanical heart valve, or thromboembolic events in the last three months) (4, 18). In such cases, the vitamin K antagonist should be discontinued five days before the procedure and, depending on the INR value, anticoagulation with a low molecular weight heparin (LMWH) should be started three days before the procedure. This, too, should be stopped 24 hours before the procedure. Most guidelines contain no recommendation favoring unfractionated heparin over LMWH (19, 22); in our opinion, the intermittent subcutaneous injection of LMWH is preferable to intravenous treatment with heparin because of its greater practicality, the possibility of outpatient bridging, and the lower hemorrhagic risk (4).

In patients who are not at high risk for thromboembolic complications (nonvalvular atrial fibrillation, CHADS₂ score < 5, thrombosis > 3 months ago), phenprocoumon should be paused for about seven days or warfarin for five days before the intervention, and an INR value below < 1.5 should be verified on the day of the intervention.

The vitamin K antagonist can usually be restarted the evening after the intervention; heparin bridging can be restarted on the first postoperative day. In all cases, however, the postprocedural management of these drugs should be directed by a specific recommendation from the physician responsible for the endoscopic procedure.

Patients receiving DOAC generally do not need, or benefit from, bridging with heparin. The few studies that have been performed on this topic have shown increased rates of bleeding complications with heparin bridging without any reduction of the rate of thromboembolism (23, 24).

Of special note in this connection is the PAUSE trial, a prospective study of a simple, standardized interruption of DOAC treatment in patients with AF, without any heparin bridging. No relevant risk of either bleeding or thrombosis was detected (25).

Before endoscopic procedures with a high risk of bleeding.

Vitamin K antagonists and direct oral anticoagulant drugs should be paused before endoscopic procedures with a high risk of bleeding.

We recommend that the last dose of apixaban, dabigatran, edoxaban, or rivaroxaban be taken three days before the intervention, with a restart 1–2 days after the intervention (figure 2). The only exception to this is dabigatran treatment in patients with an estimated glomerular filtration rate (eGFR) of 30–50 mL/h: such patients should stop taking dabigatran 5 days before the intervention because of the prolonged duration of action (25).

Figure 2.

The periprocedural management of direct oral anticoagulants for visceral medical procedures with a high risk of bleeding (modified from [4, 25]). The shaded boxes indicate the window of time in which direct oral anticoagulants can be safely restarted, depending on the postinterventional bleeding risk.

Green shading, DOAC use possible; gray shading, DOAC use should be avoided; DOAC, direct oral anticoagulants; GFR, glomular filtration rate.

Elective visceral surgery

There is no extant consensus-based classification of surgical procedures with a high or low risk of bleeding. The main factors influencing risk assessment are the feasibility of local compression of the surgical site, the size of the wound, and the extent of the local blood supply. Post-procedural bleeding is more easily controlled after superficial procedures (e.g., installation of a port system, lymph node dissection) than after intra-abdominal procedures such as hemihepatectomy, segmental liver resection, multivisceral resection for sarcoma, or retroperitoneal lymph node extirpation. The latter two operations, in particular, create a very large wound surface from which there may be persistent bleeding despite meticulous hemostasis.

The perioperative management of PAI

Elective visceral surgery.

Post-procedural bleeding is more easily controlled after superficial procedures than after intra-abdominal procedures such as hemihepatectomy, segmental liver resection, multivisceral resection for sarcoma, or retroperitoneal lymph node dissection.

Any visceral surgical procedure, even liver transplantation, can be performed under ASA without significantly increased risk. Under DAPT (ASA + clopidogrel/prasugrel/ticagrelor), any superficial operation (e.g, abscess splitting, port implantation) can also be performed. For intra-abdominal surgery, neck surgery (e.g., thyroidectomy), or surgery with a large wound surface, the relevant considerations and recommendations are analogous to those for endoscopy with increased bleeding risk. A multiplate analyzer (a device for the rapid, automated analysis of platelet aggregability under the influence of aggregation-inhibiting drugs, which can be kept, e.g., in an intensive care unit) can shorten the interval from the discontinuation of the second platelet aggregation inhibitor to the surgical procedure. In one study, multiplate analysis enabled surgery to be performed safely after an interval that was a median of 1.8 days shorter than the standard recommendation (26).

The perioperative management of OAC for elective procedures

If the thromboembolic risk is considered to outweigh than the risk of perioperative bleeding, anticoagulation should only be briefly interrupted. If OAC is vitally indicated, it can be bridged with an LWMH.

The perioperative management of platelet aggregation inhibitors.

Any visceral surgical procedure, even liver transplantation, can be performed under ASA monotherapy without significantly increased risk.

If the patient has been treated with a VKA until now, this is discontinued five days before surgery; bridging with LMWH is performed if the thromboembolic risk is high. The VKA can be restarted 3–4 days after surgery in the absence of complications.

The use of DOACs enables the performance of the planned procedure during the period in which the drug is paused. With normal renal function, a pause of 24–48 h since the last dose usually suffices (as long as there are no drug interactions that prolong the drug half-life) for the procedure to be performed with no increase of the risk of bleeding. It is now possible to measure the specific activity of each individual DOAC in serum via a modified anti-Xa assay. Preliminary evidence suggests that an apixaban level below 50 ng/mL can be considered safe for surgery (27). Bridging is not usually required in patients taking DOACs. In the RELY trial, the two patient cohorts in which dabigatran was paused with and without bridging displayed a comparable rate of thromboembolic events, but bleeding was significantly more common in the bridging group (24).

Bridging with heparin.

Bridging with heparin is only necessary when treatment with a vitamin K antagonist is paused in the setting of a high thromboembolic risk, e.g., a patient with a mechanical mitral valve prosthesis.

Acute gastrointestinal hemorrhagic complications under OAC and PAI

Gastrointestinal bleeding is among the more common complications of OAC and PAI and is not infrequently associated with high risk. Once hemodynamic stability has been achieved, endoscopy must be performed to detect and treat the source of bleeding. Good hemostasis can be achieved endoscopically even under treatment with OAC (28).In one study, for example, the rebleed rate after upper gastrointestinal bleeding was 23% in patients with an INR > 2 and 21% in patients with a normal INR during the initial endoscopic hemostasis (28). In another study, a pause in anticoagulation in order to prevent bleeding led to a statistically insignificant reduction of the rebleed rate (approximately 15% versus 20%) at the cost of a markedly higher rate of thromboembolism (8% versus 0.8%) (29).

The management of ASA.

ASA need not, and should not, be paused before surgery.

In patients who have sustained gastrointestinal bleeding while taking ASA for the secondary prevention of cardiovascular events, ASA should not be interrupted, or else the interruption should be kept as short as possible. On the other hand, discontinuation should be considered in patients who have sustained severe or recurrent bleeding while taking ASA for primary prevention. In patients at high risk of stent thrombosis who are receiving dual antiplatelet therapy (DAPT), the P2Y12 inhibitor should be interrupted only for strict indications (e.g., life-threatening bleeding) (17). Even in these cases, ASA generally should not be paused, and the P2Y12 inhibitor should be restarted as soon as possible (4, 17).

In cases of severe gastrointestinal bleeding, VKA and DOACs should be paused. The timing of the resumption of anticoagulant therapy depends on the endoscopic findings and the patient’s individual risk of thromboembolism: preferably within three days if the risk of thromboembolism is high, and within seven days if it is low. At times, short-acting substances with a readily controllable effect can also be helpful in this situation, e.g., unfractionated heparin, whose dose can be titrated on the basis of the partial thromboplastin time (PTT). The rebleed rates in certain common situations (without the additional administration of anticoagulants) are listed in the Table. Early rebleeding usually occurs in the first 3–5 days, and this would appear to justify the above-mentioned strategy in which the anticoagulant is restarted soon afterward.

Table. Rates of recurrent bleeding in major clinical entities.

Entity	Rate of early recurrent bleeding
Ulcer hemorrhage	11.5% overall, of which 55.6% occur within 3 days and 75.6% within 7 days (38)
Esophageal variceal hemorrhage	5–10% during hospitalization (median time to rebleeding, 66 hours [+/−24 hours]) (39, 40)
Diverticular hemorrhage (colon)	17.9% within 30 days, of which >90% occur within 5 days (e1)

In the case of hemodynamic instability in the setting of vital threatening gastrointestinal bleeding, antagonizing anticoagulation may be appropriate (30). In this regard, patients on VKA can be antagonized with parenteral vitamin K, with a duration of a few hours until a measurable drop in INR values in liver-healthy patients. If more rapid antagonization is required, prothrombin complex preparations (PPSB) should be used, although it should be noted that the effect of VKA lasts longer than that of PPSB and, in the absence of vitamin K administration, a renewed rise in INR values can be expected within 24 h. Such antagonization must always be weighed up, since fatal thromboembolism has been observed, especially with artificial mitral valves, even when a deranged INR value was merely reduced to the therapeutic target range with vitamin K (16, 31).

Patients receiving dual antiplatelet therapy (DAPT).

For patients receiving DAPT, multiplate analysis may be helpful in assessing the risk of bleeding. The drugs should only be paused preoperatively after consultation with a cardiologist.

Heparins can be antagonized with protamine (including low-molecular-weight heparins, but with lower efficacy); this is very rarely necessary in practice, however, because of their short half-life. The antagonization of DOACs can be considered in cases of life-threatening bleeding (3, 32). Andexanet alfa is available to antagonize the factor Xa inhibitors apixaban, rivaroxaban, and edoxaban (not approved for edoxaban; andexanet alfa must not be given before planned heparinization, because it inhibits the effect of heparin), and idarucizumab to antagonize dabigatran. The overall clinical experience with these antagonists, and the state of the evidence concerning their use, do not extend much further than the approval studies, and their cost—especially the cost of andexanet alfa—is substantial.

The effect of a P2Y12 inhibitor can be antagonized by platelet concentrate transfusion if there is a vital indications. It should be noted that ticagrelor is metabolically activated, and the metabolite reversibly inhibits platelet function. Because the metabolite remains in the circulation, ticagrelor cannot be adequately antagonized with platelet concentrates. In addition, the potentially fatal risk of stent thrombosis must be taken into account before platelet transfusion and can only be justified by the presence of a life-threatening bleeding complication (17).

In contrast, a recent randomized trial failed to show the efficacy of tranexamic acid in lessening gastrointestinal bleeding end points (independently of OAC) (33).

In general, an interventional cardiologist should always be consulted if possible whenever a pause or antagonism of OAC/PAI is under consideration, and therapeutic decisions in this regard should be made by an interdisciplinary team. Moreover, the pausing and (where applicable) restarting of vitally indicated OAH or PAI should be reevaluated by the interdisciplinary team at close intervals over the patient’s further course.

Urgent visceral medical interventions with an increased bleeding risk under OAC and PAI

The management of vitamin K antagonists.

These should be paused five days before surgery and bridged with low-molecular-weight heparin only in case of a high thromboembolic risk.

Visceral medical treatment interventions that carry a high risk of bleeding can also be needed as an emergency, e.g., endoscopic retrograde cholangiopancreatography for acute cholangitis or cholecystectomy for cholecystitis. An individual decision must then be made as to whether surgery can be postponed until better hemostasis can be achieved, and whether the antagonization of anticoagulant and/or antiplatelet drugs with vitamin K, prothrombin complex preparations, platelets, dialysis, or plasmapheresis (depending on the substances and specific antidotes) is indicated and justifiable (34).

Urgent endoscopic procedures under OAC and PAI

Endoscopic retrograde cholangiopancreatography for cholangitis is probably the most common acute endoscopic intervention with a high risk of bleeding. Sphincterotomy on a papilla that has not been treated previously carries a major risk of postinterventional hemorrhagic complications, and anticoagulation should be paused for 48–72 h after sphincterotomy whenever possible. It can be considered on an individual basis whether the risk of bleeding can be reduced by modifying the procedure, e.g., dilation of the papilla instead of sphincterotomy, and by the temporary placement of a stent. In the treatment of papillary hemorrhage under PAI or OAC, the insertion of a fully covered self-expanding metal stent (fcSEMS) for hemostasis lessens rebleeding and shortens intervention times to a statistically significant extent compared to conventional treatment (35).

Urgent visceral surgery under OAC and PAI

Patients with active bleeding or perforation of a hollow viscus need immediate surgery, so there is no opportunity to wait for the pausing or bridging of anticoagulant drugs. In principle, the general recommendations outlined above remain applicable. If the patient is taking a PAI, platelet function can be monitored with the aid of a multiplate analyzer.

Conclusion

Knowledge of the hemorrhagic risk of planned procedures, the indications for the administration of OAC or PAI and their pharmacology, and the way to estimate the thrombotic risk is essential for the periprocedural management of OAC and PAI in visceral medicine. Even though many of the recommendations presented here are often not supported by evidence from randomized trials, the available evidence from studies of cardiac and surgical patients already enables a relatively high level of safety in clinical practice and constitute a basis for the recommendations given in the current guidelines.

The management of direct oral anticoagulant drugs (DOAC).

These should be paused 24–48 hours before the procedure (GFR > 30 mL/min); their blood levels should be checked where appropriate. As a rule, bridging is unnecessary

In case of life-threatening hemorrhage….

VKA can be antagonized with PPSB/vitamin K, DOAC with specific antidotes, heparins with protamine, and platelet aggregation inhibitors with platelet concentrate.

Supplementary Material

Case illustration

A 72-year-old woman complained of progressive difficulty swallowing and was scheduled for gastroscopy. She had received an artificial aortic valve years before and was under therapeutic anticoagulation with phenprocoumon. This drug was not paused before the elective esophago-gastro-duodenoscopy, and the INR value on the day of the study was 2.3. Gastroscopy revealed a large tumor at the gastroesophageal junction. Because diagnostic esophago-gastro-duodenoscopy is still considered to carry a low risk of bleeding when mucosal biopsies are taken, extensive biopsies were taken in the same procedure in order to establish the diagnosis of the tumor.

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CME credit for this unit can be obtained via cme.aerzteblatt.de until 8 September 2023. Only one answer is possible per question. Please select the answer that is most appropriate.

Question 1

Which endoscopic procedure has a low risk of bleeding?

1. endoscopic mucosal resection of a 1.8 cm colon polyp

2. snare ablation of a 1.5 cm polyp in the duodenum

3. endoscopic submucosal dissection (ESD)

4. insertion of an esophageal stent for malignant stenosis

5. ERCP with sphincterotomy

Question 2

When is it not necessary to pause prasugrel?

1. before a polypectomy when the polyp is > 2 cm in size

2. before endoscopic retrograde cholangiopancreaticography with changing of a stent but without sphincterotomy/dilatation

3. before endoscopic submucosal dissection

4. before a percutaneous endoscopic gastrostomy

5. before endosonographic biopsy

Question 3

A patient has been under treatment with rivaroxaban for several months because of atrial fibrillation. How long before an elective esophago-gastro-duodenoscopy with mucosal biopsies should this drug be paused?

1. in the morning of the day of the study

2. one day before the study

3. two days before the study

4. three days before the study

5. it should not be paused at all

Question 4

Under which medication can most visceral surgical procedures be performed?

1. dabigatran

2. apixaban

3. rivaroxaban

4. acetylsalicylic acid

5. edoxaban

Question 5

A patient has been taking dabigatran for four months because of a pulmonary embolism. The GFR is 38 mL/min. When should she take her last dose of dabigatran before an elective endoscopic ablation early-stage gastric carcinoma?

1. the day before the study

2. two days before the study

3. three days before the study

4. on day 5 before the study

5. two weeks before the study

Question 6

What is the overall recurrence rate of ulcer hemorrhage?

1. 2%

2. 5%

3. 7%

4. 11%

5. 20%

Question 7

Which of the following scenarios best reflects a proper weighing of the need for anticoagulation against the expected risk of bleeding?

1. Phenprocoumon should not be discontinued before the elective endoscopic ablation of a large early-stage gastric carcinoma.

2. After the ablation of a large colonic polyp, phenprocoumon should not be restarted for at least seven days.

3. f the INR is 3.0 on the day of a planned esophago-gastro-duodenoscopy with mucosal biopsies, it should be corrected beforehand with a prothrombin- complex preparation.

4. Phenprocoumon should be discontinued before a planned endoscopic retrograde cholangiopancreaticography with sphincterotomy.

5. Phenprocoumon should not be discontinued before the planned ablation of a large colonic polyp.

Question 8

How long before a visceral medical procedure with a high risk of bleeding should apixaban be stopped?

1. 1 day before the procedure

2. 2 days before the procedure

3. 3 days before the procedure

4. 4 days before the procedure

5. 5 days before the procedure

Question 9

For what procedure should acetylsalicylic acid be paused if it is being given to prevent cardiovascular events?

1. (a) endoscopic retrograde cholangiopancreaticography without papillectomy

2. (b) endoscopic submucosal dissection

3. (c) endoscopic retrograde cholangiopancreaticography with papillectomy

4. (d) diagnostic endoscopy with mucosal biopsy

5. (e) diagnostic balloon enteroscopy

Question 10

What diagnosis carries a low thromboembolic risk (incidence < 5%)?

1. biological heart valve

2. mechanical heart valve

3. atrial fibrillation and mitral stenosis

4. antiphospholipid syndrome

5. JAK2 mutation

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